How exercise, genes, and bacteria are linked

Exercise is a natural activity that helps our bodies stay healthy and function well. Lack of exercise is a major cause of obesity, diabetes, and heart diseases.

Today, many of us do not get enough exercise and we eat too much, increasing our chances of being diagnosed with these diseases.

Youjie Zhang is a Ph.D. student in the Molecular Medicine track in the Department of Physiology and Pharmacology in the University of Toledo College of Medicine and Life Sciences Biomedical Science Program.

Exercise can be prescribed by your doctor, along with drugs for treating many diseases such as heart disease. However, people with low-exercise capacity are limited in the amount of exercise they are able to do. Scientific measurements can be done in the clinic to determine your capacity for exercise, which is controlled by your inherited genetics and your environment. Your environment can be changed, but your genetic inheritance cannot.

Our research challenge at the University of Toledo College of Medicine and Life Sciences is to understand how your genetic makeup contributes to your exercise capacity. I am training in the laboratory of Dr. Bina Joe, one of the leading laboratories in this field. One of our experimental systems is inbred animal models, raised in the same environment, with similar genetic makeups, to study the genetics of disease. Our research team has successfully developed two inbred rat models of exercise capacity: low-capacity runners and high-capacity runners.

We can measure exercise capacity by measuring the maximum amount of oxygen that you are able to use during hard exercising, such as running on a treadmill. We found that our rat models of high-capacity runners have significantly higher oxygen use than the low-capacity runners. In addition, similar to humans, the low-capacity runners can’t use as much oxygen and develop many diseases including obesity, high blood pressure, heart disease, depression-like behavior, and decreased memory.

We have now identified millions of genetic differences between low-capacity runners and high-capacity runners’ DNA sequences. The high-capacity runners have inherited genes in their DNA which promote both their willingness and ability to exercise. The low-capacity runners have inherited genes which do not promote their ability to exercise but promote their willingness to be couch potatoes.

These observations provide evidence for the existence of good and bad genes which can be inherited and can function to prevent or promote disease, respectively. But we still don’t understand what these good and bad genes are or how they function to prevent or promote disease.

One surprising, but important clue came from our observation that the low-capacity runners and high-capacity runners had profound differences in their gut microbiota. Gut microbiota are the tiny bacteria that live in our intestine. There are tens of trillions of bacteria in our gut, which include more than 1,000 different types of bacteria. These bacteria are now well recognized as an important factor contributing to diseases such as obesity, hypertension, and depression.

We have found that the high-capacity runners accumulate different types of bacteria in their guts compared to the low-capacity runners. For example, a group of bacteria called Actinobacteria was significantly higher in low-capacity runners compared with high-capacity runners. We then found that Actinobacteria was negatively associated with exercise capacity, and positively associated with increased body fat and depression.

Further research is underway to obtain more detailed information, with the goal of identifying all of the good and bad genes of the low-capacity runners and high-capacity runners. This evidence of interaction between your genes and your gut bacteria suggests that control of gut bacteria might be a novel therapeutic approach for the treatment of low exercise capacity or diseases due to low exercise capacity.

Youjie Zhang is a PhD student in the Molecular Medicine track in the Department of Physiology and Pharmacology in the University of Toledo College of Medicine and Life Sciences Biomedical Science Program. His research is supported by a grant from the National Institutes of Health to Dr. Bina Joe. For more information, contact [email protected] or go to utoledo.edu/med/grad/biomedical.

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